The Treatment With HBIG+GM-CSF+HBV Vaccine for Chronic Hepatitis B Patients With HBeAg Seroconversion

• Status: Unknown status
• Trial end date: 2015-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The host immunity has been generally recognized as the main factors to determine the outcome of chronic hepatitis B virus (HBV) infection; however, previous studies have shown that HBV-specific T cell and B cell function are exhausted in chronic hepatitis B (CHB) patients. Recently, It is suggested that hepatitis B surface antigen (HBsAg) may play a key role in the immune tolerance or immune exhaustion. Anti-HBV immune responses are partially recovered when patients achieved hepatitis B e antigen (HBeAg) seroconversion during antiviral therapy, and can be nearly recovered during HBsAg seroconversion. However, it is still difficult to achieve the ideal terminal, HBsAg seroconversion. For this reason, immunotherapy would be helpful to enhance the anti-HBV immunity and acquire higher HBsAg seroconversion. Here, the investigators propose a hypothesis that hepatitis B immune globin (HBIG)+granulocyte-macrophage colony-stimulating factor (GM-CSF)+HBV vaccine can enhance anti-HBV immune responses and improve HBsAg seroconversion in CHB patients who has achieved HBeAg seroconversion using nucleoside analogues treatment.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Beijing 302 Hospital
• Treatments: Vaccines

Criteria

Inclusion Criteria:

1. chronic hepatitis B patients with HBeAg seroconversion (eAg negative and eab positive)

2. age 18-50, male or female

3. HBsAg positive for at least 6 months, quantitative HBsAg <1000 IU/ml (Abbott Diagnostic, Wiesbaden, Germany)

4. HBeAg positive CHB patients who have received NAs (lamivudine, adefovir dipivoxil, entecavir, alone or in combination) treatment and achieved HBeAg seroconversion (HBeAg-, HBeAb+), HBV DNA<40 IU/ml and ALT normalization and maintained for at least 6 months.

5. Urine pregnancy test is negative in gestational age female subjects before enrollment, who can take effective contraceptive measures and agree to contraception during treatment and follow-up period.

6. Enrolled subjects should understand and sign the informed consent and comply with the requirement of the research before study.

7. Enrolled subjects should agree not to participate in other studies, and not to accept other immunomodulatory therapy during the study. Other treatments such as corticosteroids should be informed timely

Exclusion Criteria:

1. Be allergic to HBIG, GM-CSF and HBV vaccine.

2. Coinfected with other virus. Any positive for anti-hepatitis A virus (HAV), anti-hepatitis C virus (HCV), anti-hepatitis D virus (HDV), anti-hepatitis E virus (HEV) and anti-HIV.

3. Advanced cirrhosis or Child-Pugh 7 scores or above.

4. Autoimmune thrombocytopenic purpura, coronary heart disease, cerebrovascular disease, hypertension, diabetes mellitus, high myopia, history of epilepsy.

5. Other causes of liver disease, such as autoimmune liver disease, alcoholic liver disease, nonalcoholic liver disease, drug-induced liver disease and other unknown causes of chronic liver diseases.

6. Associated with other serious organic disease, mental illness, including any uncontrolled urinary, respiratory, circulation, nervous, digestive, endocrine, spirit, immune system diseases and tumor.

7. Suspected liver cancer or alpha feto protein (AFP) > 100ng/ml.

8. Neutrophil count < 2.5×109/L, or hemoglobin < 100g/L, or platelet < 80×109/L.

9. Pregnant or lactating women.

10. Allergic constitution, allergy history for blood products, known allergy to experimental drugs.

11. Alcohol or drug addiction, drug use history evidence within one year before enrolled in the study.

12. Received immunosuppressive or other immune modulators (including thymosin) or systemic cytotoxic drug 6 months before enrolled in the study.

13. Incompliance during antiviral therapy.

14. Enrolled in other clinical trials at present, and possible to be against the treatment and observation index.

15. Unable or unwilling to provide informed consent or fails to comply with the requirements of the study.

16. Other serious conditions that may hamper clinical trials.